While aggressive infection prevention efforts have significantly reduced healthcare-associated infections (HAIs) in the inpatient setting, there has been a dramatic shift of complex medical care from the hospital to nursing homes, ambulatory care settings, and even homes with visiting home health nursing care. The advent of the peripherally-inserted central venous catheter (CVC) allows for safe drug delivery without the need for hospitalization such that prolonged intravenous therapy can now be administered at home, at clinic, or by nurses at skilled nursing facilities. Nevertheless, among the 3 million Americans in U.S. nursing homes, over 67% of them experience a healthcare-associated infection, resulting in over 150,000 readmissions and over 380,000 deaths annually. Many of these infections are related to medical devices. Thus, skilled nursing facilities, oncology infusio centers, and home health nurses need to be vigilant in their care of patients at high risk for infection due to their age, comorbidities, wounds, and medical devices. Despite the fact that more preventable HAIs occur outside of hospitals than in hospitals, little is known about the burden and optimal management of HAIs in the out-of-hospital setting. Current infection prevention strategies for central line associated bloodstream infections (CLABSIs) focus on inpatient needs such as sterile insertion practices, which are not as relevant to post-insertion out-of-hospital CVC management. Furthermore, the myriad of outpatient settings results in highly variable approaches to monitoring and documenting CVC assessment and care. A comprehensive approach to CLABSI prevention in the out-of-hospital setting would include an emphasis on sterile access of the CVC, monitoring for early signs of localized inflammation at the insertion site, alerting responsible healthcare providers to problems, and triggering an efficient response protocol to remove problematic lines. This approach should be translatable across various out-of-hospital settings. The SAFER (Standardizing Assessment For Effective Response) Lines Project will evaluate a comprehensive infection prevention bundle to reduce infection and improve clinical outcomes. The bundle includes education on sterile access of CVCs, and a web-based application that enables routine use of a standardized central line insertion site assessment (CLISA) scoring tool, automated alerting of physicians for high scores, and activation of a response team to rapidly remove lines at imminent risk for CLABSI. The project will include five nursing homes, two home health agencies, and two outpatient clinic settings.